In compressing a dry particulate material into tablets, the direct compression technique is the most desirable. It employs the fewest steps and, in the case of pharmaceutical tablets containing sensitive or unstable active materials, minimizes the contact of the active ingredient with water, organic solvents or other conditions tending to adversely effect the stability thereof.
Tableting material for dry direct compression must be compressible into a tablet form, and must produce strong tablets with good tablet surfaces and good strength, particularly under the stress of automatic tableting equipment. The direct compression vehicle must be flowable into the dies of high speed tableting machines without bridging as so often occurs with fine powders. Since the amount of active material contained in a tablet is based on the weight of the tablet, weight variations caused by improper flow cannot be tolerated. The vehicle must also have good stability under normal ambient conditions so that it can be effectively compressed.
Most powdered dry materials are impractical for direct compression tableting, particularly in automatic tableting equipment because of compressive strength and/or flow problems. Some of these powders can be granulated using a wet granulation process, with or without the addition of an adhesive substance. The moistened powder is converted into a crumbly mass which is forced through a screen to reduce the material to a grain-like structure of small granules. It is then dried, milled and sieved.
The powder can also be dry granulated by precompressing the dry powder, such as, into slugs or passing the material between two compressing rollers followed by breaking the material into granular particles of uniform size.
Granular tricalcium phosphate, also known as granular tribasic calcium phosphate, and unmilled dicalcium phosphate dihydrate, also known as unmilled dibasic calcium phosphate dihydrate, are effective direct compression vehicles.
Anhydrous dicalcium phosphate, which has also been used in tableting, has generally been prepared by precipitating the product from a slurry of lime and phosphoric acid which has been heated above 80.degree. C. (see U.S. Pat. No. 3,095,269). U.S. Pat. No. 3,334,979 discloses a precipitated anhydrous dicalcium phosphate which is a hard abrasive material having a dentin abrasion (Radioactive Dentin Abrasivity) value of about 200 (see note on page 4). Precipitated anhydrous dicalcium phosphate is a fine, dense powder which must be agglomerated with a binder such as starch before it can be used in direct compression tableting.
Anhydrous dicalcium phosphate can also be prepared by driving off the water of hydration at moderately elevated temperature or on storage. The presence of free moisture accelerates dehydration, though a hard mass can be obtained (Kirk-Othmer, Encyclopedia of Chemical Technology, 3.sup.rd Edition, Vol. 17, page 446). U.S. Pat. No. 3,095,269 discloses the preparation of anhydrous dicalcium phosphate by boiling a slurry of DCPD at a pH below 5.5. At pH's near 5.5, cubic crystals of a size smaller than the diamond shaped crystals achieved at lower pH's are obtained. U.S. Pat. No. 3,095,269 further teaches that there is a problem in controlling the drying rate to effect gradual release of large quantities of chemically bound water. Excessive rate of drying tends to cause degradation of well-formed crystals due to sudden release of the water. This results in excessive break-up or fracture of the dihydrate particles, formation of fines and wide particle size distribution. U.S. Pat. No. 3,334,979 discloses that the dentin abrasion value of a dehydrated dicalcium orthophosphate dihydrate is about 60 (see Note on page 4).
Anhydrous dicalcium phosphate can also be prepared by precipitation from a mother liquor containing a combination of monoammonium phosphate with ammonium and calcium chloride (U.S. Pat. No. 3,068,067). Anhydrous dicalcium phosphate can also be prepared from a monoalkali metal phosphate solution in combination with gypsum in a mill (U.S. Pat. No. 3,353,908).
These anhydrous dicalcium phosphates alone cannot be used in dry direct compression as the particles are too fine and will not flow into the compression dies. These compounds cannot meet U.S. Pharmacopia (U.S.P.) standards without further treatment as they contain ammonium, chloride or sulfate ions. These anhydrous compositions cannot be dry granulated to make a dry direct compression tableting composition.